Dimethylformamide → (E)-tert-butyl 4-(3-(3-methoxy-3-oxoprop-1-enyl)-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

HRID 387548Notes

Reaction equation

HRID 387548 reaction equation
I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:9]=2[N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[N:4]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[N:3]=1.C(N(CC)CC)C.CN(C=O)C.[C:51]([O:55][CH3:56])(=[O:54])[CH:52]=[CH2:53]>CCOC(C)=O.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>[CH3:56][O:55][C:51](=[O:54])/[CH:52]=[CH:53]/[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:9]=2[N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[N:4]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[N:3]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 68760648tert-butyl 4-(3-iodo-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

Product 1

HCID 68763880(E)-tert-butyl 4-(3-(3-methoxy-3-oxoprop-1-enyl)-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylateYield 84%

Reagents, catalysts & solvents 4

HCID 80271Tri-o-tolylphosphineCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A 50 mL round bottom flask charged with tert-butyl 4-(3-iodo-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (500 mg, 0.8 mmol), tri(o-tolyl)phosphine (18.25 mg, 0.06 mmol), Pd2dba3 (18.3 mg, 0.02 mmol), triethylamine (334 μL, 2.4 mmol), and DMF (7 mL) was purged under N2 (3 cycles). Next, methyl acrylate (216 μL, 2.4 mmol) was added, and the mixture was stirred at 100° C. under N2 atmosphere for 18 hours. The reaction mixture was cooled to room temperature, diluted with EtOAc (50 mL) and water (100 mL) was added. The phases were separated, and the organic layer was washed with water (3×30 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was crystallized from CH3CN to provide (E)-tert-butyl 4-(3-(3-methoxy-3-oxoprop-1-enyl)-1-(4-methoxybenzyl)-5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (390 mg, 84% yield) as a solid. LCMS (APCI+) m/z 584.2 (M+H)+, Retention time=4.96 minutes.

Workup

  1. customwas purged under N2 (3 cycles)
  2. temperatureThe reaction mixture was cooled to room temperature
  3. additionwas added
  4. customThe phases were separated
  5. washthe organic layer was washed with water (3×30 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue obtained
  10. customwas crystallized from CH3CN

Sources & evidence

ORD record
ord-63d3173b2ecd43a39c21da5a76d7222d
Source dataset
uspto-grants-2013_02
Patent number
US08372842B2

Reaction notes

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